Combined effects of glutathione S-transferase M1 and T1 polymorphisms on risk of lung cancer: Evidence from a meta-analysis.

Ying Gao,Yan-Xia Sui,Ting-Ting Hu,Fei Gao,Gang Li

doi:10.18632/oncotarget.15943

Ying Gao, Yan-Xia Sui + Show 3 more

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https://doi.org/10.18632/oncotarget.15943

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Abstract

Many studies have reported an association between the glutathione S-transferase M1 null and T1 null polymorphisms and lung cancer risk. However, the combined effects of GSTM1 null and GSTT1 null polymorphisms have not been reported previously. We, therefore, performed a meta-analysis to investigate the combined effects. 40 publications with 44 case–control studies were selected in the meta-analysis, including 13,706 cases and 13,093 controls. Significant association was observed between the combined effects of GSTM1 and GSTT1 polymorphisms and lung cancer risk when all the eligible studies were pooled into the meta-analysis. When we performed subgroup analysis, significantly increased lung cancer risk was observed in Caucasians (− − vs. + +: OR = 1.23, 95% CI: 1.07 to 1.41), Asians (− − vs.− +: OR = 1.24, 95% CI: 1.10 to 1.41; recessive model: OR = 1.45, 95% CI: 1.19 to 1.77; dominant model: OR = 1.53, 95% CI: 1.24 to 1.90), Indians (− − vs. + +: OR = 2.53, 95% CI: 1.61 to 3.98; recessive model: OR = 1.69, 95% CI: 1.07 to 2.67; dominant model: OR = 2.11, 95% CI: 1.36 to 3.28), hospital-based studies, and population-based studies. In summary, this meta-analysis indicates that the combined effects of the GSTM1 and GSTT1 polymorphisms are associated with increased lung cancer risk in Asians, Caucasians, and Indians.

Highlights

Lung cancer has become the most common cancer and the leading cause of cancer death in the world [1]
Significant association was observed between the combined effects of glutathione S-transferase M1 (GSTM1) and GSTT1 polymorphism and lung cancer risk
Gene polymorphism factor has been reported to be an important factor which increases the susceptibility of lung cancer

Summary

Introduction

Lung cancer has become the most common cancer and the leading cause of cancer death in the world [1]. There were about 219,440 lung cancer cases and 159,390 deaths expected in the United States in 2009 [2]. Not all smokers develop lung cancer, which indicates that other causes, including genetic susceptibility, may contribute to development of lung cancer [5,6]. Possible lung cancer susceptibility genes have been sought among tumor suppressor genes, DNA repair genes, and genes encoding phase I and phase II enzymes [7]. GSTs can be classified into at least four genetically distinct groups including Glutathione S-transferase M1(GSTM1) and Glutathione S-transferase T1(GSTT1) [10]. GSTM1 and GSTT1 are www.impactjournals.com/oncotarget two of the most important GST variants. Individuals with the homozygous deletion of the GSTM1 and GSTT1 locus (GSTM1 null and GSTT1 null) have no enzymatic functional activity [11]

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